5ezx: Difference between revisions
New page: '''Unreleased structure''' The entry 5ezx is ON HOLD Authors: Banner, D., Benz, J., Stihle, M., Kuglstatter, A. Description: CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH {(1R,2R)-2-[(R)... |
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==CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH {(1R,2R)-2-[(R)-2-Amino-4-(4-difluoromethoxy-phenyl)-4,5-dihydro-oxazol-4-yl]-cyclopropyl}-(5-chloro-pyridin-3-yl)-methanone== | |||
<StructureSection load='5ezx' size='340' side='right'caption='[[5ezx]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ezx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EZX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5T5:[(1~{R},2~{R})-2-[(4~{S})-2-AZANYL-4-[4-[BIS(FLUORANYL)METHOXY]PHENYL]-5~{H}-1,3-OXAZOL-4-YL]CYCLOPROPYL]-(5-CHLORANYLPYRIDIN-3-YL)METHANONE'>5T5</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ezx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezx OCA], [https://pdbe.org/5ezx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ezx RCSB], [https://www.ebi.ac.uk/pdbsum/5ezx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction. | |||
A Real-World Perspective on Molecular Design.,Kuhn B, Guba W, Hert J, Banner D, Bissantz C, Ceccarelli S, Haap W, Korner M, Kuglstatter A, Lerner C, Mattei P, Neidhart W, Pinard E, Rudolph MG, Schulz-Gasch T, Woltering T, Stahl M J Med Chem. 2016 Feb 24. PMID:26878596<ref>PMID:26878596</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ezx" style="background-color:#fffaf0;"></div> | ||
[[Category: Benz | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Banner D]] | |||
[[Category: Benz J]] | |||
[[Category: Kuglstatter A]] | |||
[[Category: Stihle M]] | |||
Latest revision as of 11:37, 12 July 2023
CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH {(1R,2R)-2-[(R)-2-Amino-4-(4-difluoromethoxy-phenyl)-4,5-dihydro-oxazol-4-yl]-cyclopropyl}-(5-chloro-pyridin-3-yl)-methanoneCRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH {(1R,2R)-2-[(R)-2-Amino-4-(4-difluoromethoxy-phenyl)-4,5-dihydro-oxazol-4-yl]-cyclopropyl}-(5-chloro-pyridin-3-yl)-methanone
Structural highlights
FunctionBACE1_HUMAN Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.[1] [2] Publication Abstract from PubMedWe present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction. A Real-World Perspective on Molecular Design.,Kuhn B, Guba W, Hert J, Banner D, Bissantz C, Ceccarelli S, Haap W, Korner M, Kuglstatter A, Lerner C, Mattei P, Neidhart W, Pinard E, Rudolph MG, Schulz-Gasch T, Woltering T, Stahl M J Med Chem. 2016 Feb 24. PMID:26878596[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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